Microfluidics refers to a set of technologies involving the flow of fluids through channels having at least one linear interior dimension, such as depth or radius, of less than 1 mm. It is possible to create microscopic equivalents of bench-top laboratory equipment such as beakers, pipettes, incubators, electrophoresis chambers, and analytical instruments within the channels of a microfluidic device. Since it is also possible to combine the functions of several pieces of equipment on a single microfluidic device, a single microfluidic device can perform a complete analysis that would ordinarily require the use of several pieces of laboratory equipment. A microfluidic device designed to carry out a complete chemical or biochemical analyses is commonly referred to as a micro-Total Analysis System (μ-TAS) or a “lab-on-a chip.”
A lab-on-a-chip type microfluidic device, which can simply be referred to as a “chip,” is typically used as a replaceable component, like a cartridge or cassette, within an instrument. The chip and the instrument form a complete microfluidic system. The instrument can be designed to interface with microfluidic devices designed to perform different assays, giving the system broad functionality. For example, the commercially available Agilent 2100 Bioanalyzer system can be configured to perform four different types of assays—namely DNA (deoxyribonucleic acid), RNA (ribonucleic acid), protein and cell assays—by simply placing the appropriate type of chip into the instrument.
Microfluidic devices designed to carry out complex analyses will often have complicated networks of intersecting channels. Performing the desired assay on such chips will often involve separately controlling the flows through certain channels, and selectively directing flows from certain channels through channel intersections. Fluid flow through complex interconnected channel networks can be accurately controlled by applying a combination of external driving forces to the microfluidic device. The use of multiple electrical driving forces to control the flow through complicated networks of intersecting channels in a microfluidic device is described in U.S. Pat. No. 6,010,607, which is incorporated herein by reference in its entirety. The use of multiple pressure driving forces to control flow through complicated networks of intersecting channels in a microfluidic device is described in U.S. Pat. No. 6,915,679, which is incorporated herein by reference in its entirety.
The use of multiple electrical or pressure driving forces to control flow in a chip provides extremely precise flow control. In many microfluidic devices, this precise flow control is employed to define an exact volume of a sample to be delivered to a capillary electrophoresis (CE) separation process. For example, in previously cited U.S. Pat. No. 6,010,607, electrical driving forces create a flow pattern that constrains a flow of sample material into a precisely defined volume. Alternatively, U.S. Pat. No. 6,423,198 describes a method in which a volume of sample material is defined by the distance along a channel between an inlet to the channel and an outlet from the channel.
The resolution and sensitivity of CE separation processes can be enhanced by concentrating the sample before the sample is subjected to the CE process. Concentrating a sample can be used to increase the concentration of sample components to more detectable levels. The field amplified sample stacking (FASS) process is one method of concentrating a sample before the sample is subject to a CE separation process. The combination of FASS and CE is discussed in Jung, B., Bharadwaj, R. and Santiago, J. G., “Thousand-fold signal increase using field-amplified sample stacking for on-chip electrophoresis,” Electrophoresis, Vol. 24, pp. 3476-3483 2003, which is incorporated by reference in its entirety. Another process that can be used to concentrate a sample before CE is isotachophoresis (ITP). The combination of ITP and CE is discussed in U.S. Published Patent Application No. 2005/0133370, which is incorporated by reference in its entirety, and U.S. Pat. No. 6,818,113.
The primary motivation for concentrating a sample before it is subject to a separation process such as CE appears to be to make low-concentration components of the sample easier to detect. It does not appear to be recognized, however, that concentration-changing processes could also be employed to manipulate the concentrations of reacting chemicals within a microfluidic device. Since the rates of chemical reactions are typically determined by the concentration of one or more reactants, being able to manipulate the concentration of the rate-limiting reactant(s) could lead to precise control of reaction rates within a microfluidic device.
It is thus an object of the present invention to manipulate the concentration of one or more reactants within a microfluidic device.
It is a further object of the present invention to couple the ability to control reactant concentration with other known methods of increasing the rate of chemical reactions within a microfluidic device.
These and further objects will be more readily appreciated when considering the following disclosure and appended claims.